Efficacy and Safety Study of Mepolizumab in Subjects With Moderate to Severe Atopic Dermatitis
- Conditions
- Dermatitis, Atopic
- Interventions
- Registration Number
- NCT03055195
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Mepolizumab is a humanized Immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that acts on Interleukin-5 (IL-5), which is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils; thereby reducing the production and survival of eosinophils which may be therapeutic in subjects with atopic dermatitis (AD). This study will investigate the efficacy and safety of mepolizumab (100 milligram \[mg\] subcutaneous \[SC\] administered every 4 weeks) compared with placebo in adult subjects with moderate to severe atopic dermatitis (AD). Subjects will be randomized 1:1 to either placebo SC or mepolizumab SC. The study will comprise of a pre-screening period of up to approximately 4 weeks, a screening period of up to 2 weeks, followed by a 16-Week study treatment period (16 weeks with the last dose of study treatment at Week 12) and follow-up period of up to 4-week. The total duration of subject participation will be approximately 26 weeks. (Note: For subjects, who may need to stop treatment with a biologic, the total Pre-Screening and Screening period may last up to 20 weeks and total duration of participation in the study may be up to 40 weeks).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 34
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Mepolizumab Mepolizumab 100 mg Eligible subjects will receive mepolizumab 100 mg subcutaneously every 4 weeks on Day 1, Week 4, Week 8, and Week 12 Placebo Placebo matching mepolizumab Eligible subjects will receive matching placebo subcutaneously every 4 weeks on Day 1, Week 4, Week 8, and Week 12
- Primary Outcome Measures
Name Time Method Number of Participants With an Investigator's Global Assessment (IGA) Score of 0 or 1 and at Least a 2- Grade Improvement at Week 16 Week 16 The IGA is a clinical tool for assessing the current state/severity of a participant's atopic dermatitis . It is a static 5-point morphological assessment of overall disease severity determined by the investigator, sub-investigator, or trained healthcare professional with required qualifications on a scale of 0 to 4 where, 0-clear, 1-almost clear, 2-mild, 3-moderate, and 4- severe. Higher score indicates severity of disease. A responder is defined as a participant who had an IGA score of 0 or 1 and a minimum 2-grade improvement from Baseline. Number of participants with IGA score of 0 or 1 and at least a 2- grade improvement at Week 16 was presented.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Hematology Parameter: Erythrocytes Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Blood samples were collected to analyze the hematology parameter: Erythrocytes. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Mean Percentage Change in Eczema Area and Severity Index (EASI) Score From Baseline to Each Study Visit Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 EASI scoring system is a standardized clinical tool for the assessment of atopic dermatitis that takes into account overall extent of the percent body surface area (% BSA) involved and severity scores for each clinical signs (erythema, induration/papulation, excoriation, and lichenification). Severity scores were graded on a 4-point scale, 0(absent) to 3(severe) for each body regions (head and neck, upper extremities, lower extremities, and trunk). The severity scores for each signs were summed for each region and multiplied by the % BSA area score and by the appropriate proportionality multiplier (for participants \>=8 years of age, 0.1 for head, 0.2 upper extremities, 0.3 for trunk and 0.4 for lower extremities) to generate a regional EASI score. The regional EASI scores were then summed to yield the final EASI score. Baseline is defined as latest pre-dose assessment. Percent change from Baseline is Post-Baseline Visit Value minus Baseline, divided by Baseline and multiplied by 100.
Number of Participants With an IGA Score of 0 or 1 and at Least a 2-grade Improvement at Each Study Visit Weeks 4, 8, 12, 16 and 20 The IGA is a clinical tool for assessing the current state/severity of a participant's atopic dermatitis . It is a static 5-point morphological assessment of overall disease severity determined by the investigator, sub-investigator, or trained healthcare professional with required qualifications on a scale of 0 to 4 where, 0-clear, 1-almost clear, 2-mild, 3-moderate, and 4- severe. Higher score indicates severity of disease. A Responder is defined as a participant who had an IGA score of 0 or 1 and a minimum 2-grade improvement from Baseline. Participants withdrawn early from the study were assigned to be a non-responder for all weeks after withdrawal. Number of participants with IGA score of 0 or 1 and at least a 2- grade improvement at each study visit (Weeks 4, 8, 12, 16 and 20) is presented.
Number of Participants With On-treatment Adverse Events (AEs), Serious Adverse Events (SAEs) and Non-serious Adverse Events (nSAEs) Up to Week 20 An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. On-treatment AES were reported on or after treatment start date and on or before treatment stop date (plus 28 days). Number of participants with AEs, SAEs and nSAEs is presented.
Number of Participants With On-treatment AEs of Special Interest Reported as Local Site Injection Reaction and Systemic Reactions Up to Week 20 An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with local site injection reaction and systemic reactions were reported.
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils and Platelets. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Blood samples were collected to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Hematology Parameter: Hematocrit Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Blood samples were collected to analyze the hematology parameter: Hematocrit. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Hematology Parameter: Hemoglobin Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Blood samples were collected to analyze the hematology parameter: Hemoglobin. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) Baseline (Day 1) and Weeks 4, 8, 12, and 16 Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST . Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Chemistry Parameters: Albumin and Protein Baseline (Day 1) and Weeks 4, 8, 12, and 16 Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Chemistry Parameters: Bilirubin, Creatinine, Direct Bilirubin Baseline (Day 1) and Weeks 4, 8, 12, and 16 Blood samples were collected to analyze the chemistry parameters: Bilirubin, Creatinine and Direct Bilirubin. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea Baseline (Day 1) and Weeks 4, 8, 12, and 16 Blood samples were collected to analyze the chemistry parameters: Calcium, Glucose, Potassium, Sodium and Urea. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Number of Participants With Worst Post Baseline Potential Clinical Importance (PCI) Value for Hematology Parameters Up to Week 20 Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes and platelets. PCI ranges were \< 0.201 or \>0.599 proportion of red blood cells in blood for hematocrit, \<71 or \>199 grams per liter for hemoglobin, \<31 or \>1499 Giga cells per liter for platelets and for leukocytes \< 1.1 Giga cells per liter. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants with laboratory value category "To Low" and "To High" were presented. Only those parameters having worst post-Baseline PCI values were presented. Day 1 was considered as Baseline.
Number of Participants With Worst Post Baseline PCI Value for Chemistry Parameters Up to Week 16 Blood samples were collected from participants for analysis of following clinical chemistry parameters: ALT, Calcium, glucose, Potassium and sodium. PCI ranges were \>143 units per liter (U/L) for ALT (Age category: 3-12 years) and \>239 U/L for ALT (Age category: 13+ years), \<1.50 or \>3.24 mmol/L for calcium, \< 2.2 or \> 27.8 mmol/L for glucose, \<2.8 or \>6.5 mmoL/L for potassium , and \<120 or \>160 mmoL/L for sodium. Participants were counted in the worst case category that their value changes to (low, normal , or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Only those parameters having worst post-Baseline PCI values were presented. Day 1 was considered as Baseline.
Change From Baseline in PR Interval, QRS Duration, QT Interval and QT Interval Corrected for Heart Rate According to Fridericia's Formula (QTcF) Baseline (Screening) and Weeks 4, 16 Triplicate 12-lead electrocardiograms (ECG) were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Screening was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Number of Participants With Worst Post Baseline PCI Value for Vital Signs Up to Week 20 Blood samples were collected from participants for analysis of following vital signs parameters: DBP, Pulse rate and SBP. PCI ranges were \<85 or \>160 mmHg for SBP, \<45 or \>100 mmHg for DBP and \< 40 or \> 110 beats per minute for Pulse rate. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants with vital signs value category "To Low" and "To High" were presented. Only those parameters having worst post-Baseline PCI values are presented. Day 1 was considered as Baseline.
Change From Baseline in Vital Signs: Pulse Rate Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Change From Baseline in Vital Signs: Temperature Baseline (Day 1) and Weeks 4, 8, 12, 16 and 20 Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day 1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Number of Participants With Abnormal Findings for ECG Parameters Week 4 and Week 16 Triplicate 12-lead ECG were obtained to measure ECG parameters. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Number of Participants With Any Time Post Baseline Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies Response Up to Week 20 Blood samples were collected for the determination of anti-mepolizumab antibodies at the specified visits. The number of participants with anti-mepolizumab binding antibodies and neutralizing antibodies response at Any Time Post Baseline has been presented. Neutralizing antibodies response assay result have been only presented for participants with positive anti-drug antibody assay. Day 1 was considered as Baseline.
Trial Locations
- Locations (1)
GSK Investigational Site
🇨🇦Quebec, Canada